Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder. Mouse models have been indispensable to offer insights into the crucial pathophysiology of AD. However, the majority of mouse models are developed by overexpression of familial AD genetic mutations such as APP and PS1/2, which account for only a small percentage of AD cases. In this manuscript, we summarized the development of a novel late-onset sporadic AD model, namely Thy1-ApoE4/C/EBPb double transgenic mouse, carrying no genetic mutations but displaying key AD pathologies in an age-dependent manner. This mouse model is developed based on the C/EBPb / AEP pathway that plays a crucial role in driving AD development.